Collagen gel structures have many benefits as a drug delivery and tissue engineering system. They have been used for many years in plastic surgery as an injectable implant because they are visco-elastic and can flow under stress. However, the downside of collagen gels is the high pore size (tens of nanometers), which makes controlled release difficult without attaching the molecule to collagen. Randomly oriented gels are also too weak to bear tensile loads or for surgical manipulation. In addition, while the mechanical properties of collagen gels can be either altered by covalent or non-covalent cross-linking (heat, chemicals, or UV irradiation) or combined with other composites to increase strength. The effect of these techniques are not straight forward, and some can lead to the degradation of collagen or have an adverse cytotoxicity on cell growth.
Unoriented collagen gels have been produced as cell culture substrate for almost fifty years. They can be produced by warming a neutralized solution of collagen to physiological temperature. One method for creating an oriented collagen gel is the use of a high strength magnetic field to induce the orientation of the collagen fibers during fibrillogenesis. This method requires the use of a strong magnetic field, 0.5-5 Tesla depending on gel dimensions, making it impractical for commercial production. Oriented collagen gels were produced in a microfluidic channel. In this method, a solution of alkaline collagen was allowed to polymerize in PDMS channels 10-400 microns in width. The fluids were briefly subjected to a flow velocity of 5-10 mm/s as they entered the channel with a stationary depositing device. The flow rates in this example, were not significant enough to manipulate the orientation of the collagen molecules. The invention provides new techniques to create oriented collagen gels.